SUMMARY The menopausal transition is a period of vulnerability during which many women experience sleep difficulties and cognitive deficits. In addition, as many as 75% of women suffer from hot flashes which can severally disrupt quality of life. The prevalence and severity of co-occurring hot flashes, sleep disturbances and cognitive impairment is a major public health issue for midlife women. Yet, the potential relationships among these three symptoms are understudied and poorly understood. The lack of an appropriate animal model has largely contributed to the slow progress in understanding this major health issue. This exploratory proposal will determine the validity of a small primate, the common marmoset (Callithrix jacchus), as a model to study the three main symptoms experienced by women at menopause. The marmoset has high potential as such a model: its size is well suited for the surgical implantation of telemetry systems that record sleep patterns and core body temperature without interfering with the animal's normal behavior; its sleep architecture is very similar to that of humans, and it is capable of performing complex cognitive tasks. This project will determine whether manipulations of the estrogenic milieu in the surgically menopausal middle-aged marmoset induce changes in sleep patterns, cognition, and thermoregulation that are consistent with menopausal symptoms. These questions will be addressed in three Specific Aims: (1) to determine whether estradiol (E2) manipulations induce changes in sleep patterns (2) to determine whether E2 manipulations induce changes in cognitive performance (3) to determine whether E2 manipulations induce changes in thermoregulation. Observations from this study should establish the surgically menopausal marmoset as a valid primate model for the three major menopausal symptoms experienced by women. These data will set the stage for further studies designed to elucidate the potential interactions between sleep disturbances, hot flashes and cognitive impairment and their underlying mechanisms. Ultimately, these studies should lead to the development of novel, non-estrogenic therapeutics for the many women suffering from menopausal symptoms.